Jingwen Yao1,2,3, Caleb Hock Pang Tan4, Jacob Schlossman5, Ararat Chakhoyan1,2, Catalina Raymond1,2, Whitney B Pope2, Noriko Salamon2, Albert Lai6,7, Matthew Ji6,7, Phioanh L Nghiemphu6,7, Linda M Liau8, Timothy F Cloughesy6,7, Benjamin M Ellingson9,10,11,12,13. 1. UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, University of California, Los Angeles, Los Angeles, CA, USA. 2. Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. 3. Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, CA, USA. 4. Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, USA. 5. Interdepartmental Program for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA. 6. UCLA Neuro-Oncology Program, University of California, Los Angeles, Los Angeles, CA, USA. 7. Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. 8. Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. 9. UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, University of California, Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu. 10. Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu. 11. Department of Bioengineering, Henry Samueli School of Engineering and Applied Science, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu. 12. UCLA Neuro-Oncology Program, University of California, Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu. 13. Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, 924 Westwood Blvd., Suite 615, Los Angeles, CA, 90024, USA. bellingson@mednet.ucla.edu.
Abstract
PURPOSE: The objective of the current study was to explore the efficacy of using pH-weighted amine CEST-EPI as a potential non-invasive imaging biomarker for treatment response and/or failure in recurrent GBM patients treated with bevacizumab. METHOD: A total of 11 patients with recurrent GBM treated with bevacizumab were included in this prospective study. CEST-EPI, perfusion MRI, and standardized anatomic MRI were obtained in patients before and after bevacizumab administration. CEST-EPI measures of magnetization transfer ratio asymmetry (MTRasym) at 3 ppm were used for pH-weighted imaging contrast. Multiple measures were examined for their association with progression-free survival (PFS). RESULT: Tumor acidity, measured with MTRasym at 3 ppm, was significantly reduced in both contrast enhancing and non-enhancing tumor after bevacizumab (p = 0.0002 and p < 0.00001, respectively). The reduction in tumor acidity in both contrast enhancing and non-enhancing tumor was linearly correlated with PFS (p = 0.044 and p = 0.00026, respectively). In 9 of the 11 patients, areas of residual acidity were localized to areas of tumor recurrence, typically around 2 months prior to radiographic progression. Univariate (p = 0.006) and multivariate Cox regression controlling for age (p = 0.009) both indicated that change in tumor acidity (ΔMTRasym at 3 ppm) was a significant predictor of PFS. CONCLUSIONS: This pilot study suggests pH-weighted amine CEST MRI may have value as a non-invasive, early imaging biomarker for bevacizumab treatment response and failure. Early decreases MTRasym at 3.0 ppm in recurrent GBM after bevacizumab may be associated with better PFS. Residual or emerging regions of acidity may colocalize to the site of tumor recurrence.
PURPOSE: The objective of the current study was to explore the efficacy of using pH-weighted amineCEST-EPI as a potential non-invasive imaging biomarker for treatment response and/or failure in recurrent GBM patients treated with bevacizumab. METHOD: A total of 11 patients with recurrent GBM treated with bevacizumab were included in this prospective study. CEST-EPI, perfusion MRI, and standardized anatomic MRI were obtained in patients before and after bevacizumab administration. CEST-EPI measures of magnetization transfer ratio asymmetry (MTRasym) at 3 ppm were used for pH-weighted imaging contrast. Multiple measures were examined for their association with progression-free survival (PFS). RESULT: Tumor acidity, measured with MTRasym at 3 ppm, was significantly reduced in both contrast enhancing and non-enhancing tumor after bevacizumab (p = 0.0002 and p < 0.00001, respectively). The reduction in tumor acidity in both contrast enhancing and non-enhancing tumor was linearly correlated with PFS (p = 0.044 and p = 0.00026, respectively). In 9 of the 11 patients, areas of residual acidity were localized to areas of tumor recurrence, typically around 2 months prior to radiographic progression. Univariate (p = 0.006) and multivariate Cox regression controlling for age (p = 0.009) both indicated that change in tumor acidity (ΔMTRasym at 3 ppm) was a significant predictor of PFS. CONCLUSIONS: This pilot study suggests pH-weighted amine CEST MRI may have value as a non-invasive, early imaging biomarker for bevacizumab treatment response and failure. Early decreases MTRasym at 3.0 ppm in recurrent GBM after bevacizumab may be associated with better PFS. Residual or emerging regions of acidity may colocalize to the site of tumor recurrence.
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